Chromatin dynamics in host-gut microbiome interactions in the mouse colon

This study aimed to gain a deeper understanding of the epigenetic interactions, functions and mechanisms of the host colon cells that are influenced by the gut microbiome. With the potential to contribute toward understanding the development of inflammatory bowel disease (IBD) and its co-morbidities and the increased risk of colorectal cancer (CRC), this knowledge, could facilitate and develop prevention strategies and possibly treatment. The interactions between the chromatin dynamics and the gut microbiome are very complex and sophisticated. There are many pathways that facilitate the smooth running of the gut and protect it from external invaders and internal mutations. I have been able to gain some insight into the beneficial effect of SCFAs with DSS-induced colitis, suggesting a new potential pre-treatment for IBD patients through the use of crotonic acid supplemented into their diets. I have been able to describe the overall effects of the microbiome on histone modifications, specifically histone crotonylation, giving insight into the involvement crotonylation may have with tumour promotion and suppression, and regulation of immune responses. I have also established some of the roles the chromatin remodeller Smarcad1 has on histone modifications, predominantly influencing the activity of H3K9ac and H3K9cr, highlighting links to the maintenance of the gut and potential regulation of tumour development and suppression. Finally, I have been able to recognise a potential link between Smarcad1 and the microbiome with the notable changes Smarcad1 has on H3K9cr and the significant increase of this histone modification with recolonised germfree mice. Understanding the functions of these host-microbiome interactions has provided potentially new pathways of investigation to develop prevention measures and potential therapeutic targets for IBD and CRC.